Immune checkpoint modulators in cancer immunotherapy: Recent advances and combination rationales

As a new hallmark of cancer, immune surveillance evading plays a critical role in carcinogenesis. Through modulating the immune checkpoints, immune cells in tumor microenvironment can be harnessed to battle cancer cells. In recent years, the administration of anti-CTLA or/and anti-PD-1/L1 antibody h...

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Published inCancer letters Vol. 456; pp. 23 - 28
Main Authors Fan, Li, Li, Yue, Chen, Jia-Yu, Zheng, Yong-Fa, Xu, Xi-Ming
Format Journal Article
LanguageEnglish
Published Ireland Elsevier B.V 01.08.2019
Elsevier Limited
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Abstract As a new hallmark of cancer, immune surveillance evading plays a critical role in carcinogenesis. Through modulating the immune checkpoints, immune cells in tumor microenvironment can be harnessed to battle cancer cells. In recent years, the administration of anti-CTLA or/and anti-PD-1/L1 antibody has exhibited unexpected antitumor effect in multiple types of cancer, motivating the researchers to find more potential immune checkpoints as clinical targets. A wealth of clinical trials have been done to evaluate the safety and efficacy of monotherapy or combination therapy with immune checkpoint modulators. However, there still exist problems such as low response rate and adverse events in the clinical, which in turn leads us to the basic study. The better understanding of the crosstalk between the immune cells and the cancer cells within the microenvironment may inspire us new ideas for cancer treatment. In this review, we mainly summarize the recent advances in application of immune checkpoint modulators and the combination rationales, and discuss the problems existing in the precision therapy with immune checkpoint modulators. •The application of anti-PD and anti-CTLA immune checkpoint modulators alone or in combination has exhibited unexpected antitumor effect in multiple types of cancer.•There are a lot of clinical studies of other checkpoint modulators, including the inhibitory modulators (LAG-3 inhibitor) and stimulatory modulators (agonists of CD27, OX-40, CD40, ICOS, 4-1BB and GITR), but their efficacy is still pending.•Despite the rapid progress in cancer immunotherapy, there still exist some problems to achieve precision therapy with immune checkpoint modulators.
AbstractList As a new hallmark of cancer, immune surveillance evading plays a critical role in carcinogenesis. Through modulating the immune checkpoints, immune cells in tumor microenvironment can be harnessed to battle cancer cells. In recent years, the administration of anti-CTLA or/and anti-PD-1/L1 antibody has exhibited unexpected antitumor effect in multiple types of cancer, motivating the researchers to find more potential immune checkpoints as clinical targets. A wealth of clinical trials have been done to evaluate the safety and efficacy of monotherapy or combination therapy with immune checkpoint modulators. However, there still exist problems such as low response rate and adverse events in the clinical, which in turn leads us to the basic study. The better understanding of the crosstalk between the immune cells and the cancer cells within the microenvironment may inspire us new ideas for cancer treatment. In this review, we mainly summarize the recent advances in application of immune checkpoint modulators and the combination rationales, and discuss the problems existing in the precision therapy with immune checkpoint modulators. •The application of anti-PD and anti-CTLA immune checkpoint modulators alone or in combination has exhibited unexpected antitumor effect in multiple types of cancer.•There are a lot of clinical studies of other checkpoint modulators, including the inhibitory modulators (LAG-3 inhibitor) and stimulatory modulators (agonists of CD27, OX-40, CD40, ICOS, 4-1BB and GITR), but their efficacy is still pending.•Despite the rapid progress in cancer immunotherapy, there still exist some problems to achieve precision therapy with immune checkpoint modulators.
As a new hallmark of cancer, immune surveillance evading plays a critical role in carcinogenesis. Through modulating the immune checkpoints, immune cells in tumor microenvironment can be harnessed to battle cancer cells. In recent years, the administration of anti-CTLA or/and anti-PD-1/L1 antibody has exhibited unexpected antitumor effect in multiple types of cancer, motivating the researchers to find more potential immune checkpoints as clinical targets. A wealth of clinical trials have been done to evaluate the safety and efficacy of monotherapy or combination therapy with immune checkpoint modulators. However, there still exist problems such as low response rate and adverse events in the clinical, which in turn leads us to the basic study. The better understanding of the crosstalk between the immune cells and the cancer cells within the microenvironment may inspire us new ideas for cancer treatment. In this review, we mainly summarize the recent advances in application of immune checkpoint modulators and the combination rationales, and discuss the problems existing in the precision therapy with immune checkpoint modulators.
As a new hallmark of cancer, immune surveillance evading plays a critical role in carcinogenesis. Through modulating the immune checkpoints, immune cells in tumor microenvironment can be harnessed to battle cancer cells. In recent years, the administration of anti-CTLA or/and anti-PD-1/L1 antibody has exhibited unexpected antitumor effect in multiple types of cancer, motivating the researchers to find more potential immune checkpoints as clinical targets. A wealth of clinical trials have been done to evaluate the safety and efficacy of monotherapy or combination therapy with immune checkpoint modulators. However, there still exist problems such as low response rate and adverse events in the clinical, which in turn leads us to the basic study. The better understanding of the crosstalk between the immune cells and the cancer cells within the microenvironment may inspire us new ideas for cancer treatment. In this review, we mainly summarize the recent advances in application of immune checkpoint modulators and the combination rationales, and discuss the problems existing in the precision therapy with immune checkpoint modulators.As a new hallmark of cancer, immune surveillance evading plays a critical role in carcinogenesis. Through modulating the immune checkpoints, immune cells in tumor microenvironment can be harnessed to battle cancer cells. In recent years, the administration of anti-CTLA or/and anti-PD-1/L1 antibody has exhibited unexpected antitumor effect in multiple types of cancer, motivating the researchers to find more potential immune checkpoints as clinical targets. A wealth of clinical trials have been done to evaluate the safety and efficacy of monotherapy or combination therapy with immune checkpoint modulators. However, there still exist problems such as low response rate and adverse events in the clinical, which in turn leads us to the basic study. The better understanding of the crosstalk between the immune cells and the cancer cells within the microenvironment may inspire us new ideas for cancer treatment. In this review, we mainly summarize the recent advances in application of immune checkpoint modulators and the combination rationales, and discuss the problems existing in the precision therapy with immune checkpoint modulators.
Author Zheng, Yong-Fa
Fan, Li
Li, Yue
Xu, Xi-Ming
Chen, Jia-Yu
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Keywords Ani-PD-1/L1
Immune checkpoint modulators
Combinational immunotherapy
Anti-CTLA-4
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Snippet As a new hallmark of cancer, immune surveillance evading plays a critical role in carcinogenesis. Through modulating the immune checkpoints, immune cells in...
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SubjectTerms Ani-PD-1/L1
Animals
Anti-CTLA-4
Antigens
Antineoplastic Agents, Immunological - adverse effects
Antineoplastic Agents, Immunological - therapeutic use
Antineoplastic Combined Chemotherapy Protocols - adverse effects
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Antitumor activity
Apoptosis
Autoimmune diseases
Biomarkers
Cancer
Cancer immunotherapy
Carcinogenesis
Cell Communication
Clinical trials
Combinational immunotherapy
Editing
Fibroblasts
Homeostasis
Humans
Immune checkpoint
Immune checkpoint modulators
Immunoglobulins
Immunomodulation
Immunosurveillance
Immunotherapy
Ligands
Lymphocytes
Melanoma
Molecular Targeted Therapy
Neoplasms - drug therapy
Neoplasms - immunology
Neoplasms - metabolism
Neoplasms - pathology
PD-1 protein
Proteins
Response rates
Signal Transduction
Treatment Outcome
Tumor Microenvironment
Tumor necrosis factor-TNF
Title Immune checkpoint modulators in cancer immunotherapy: Recent advances and combination rationales
URI https://www.clinicalkey.com/#!/content/1-s2.0-S0304383519302149
https://dx.doi.org/10.1016/j.canlet.2019.03.050
https://www.ncbi.nlm.nih.gov/pubmed/30959079
https://www.proquest.com/docview/2226706403
https://www.proquest.com/docview/2206231738
Volume 456
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